The objectives of this research project are to describe those biochemical mechanisms which regulate the formation, secretion, and metabolism of lipids and lipoproteins by the liver, and to describe the role of the liver in the control of blood lipids. We propose during the coming year to examime how different fatty acids affect the lipid composition and physical properties of the very low density lipoproteins (VLDL) and other lipoproteins produced by the liver, and the hepatic secretion of triglyceride, phospholipid, and cholesterol (in the VLDL). Since the quantity and structure of the FFA available to the liver determine the rate of secretion of the triglyceride and other lipids of the VLDL, we will examine the proposition that FFA may be a regulator of hepatic biosynthesis of cholesterol. In addition, we will continue our studies on the hormonal regulation of these processes, particularly on effects of antiinsulin serum and insulin. The biochemical reasons for the profound difference in hepatic triglyceride metabolism between livers from male and female animals will be investigated, and whether these differences are mediated by gonadal steroids. Finally we will continue our attempts to improve the methodology for isolation and analysis of lipoproteins from plasma of man and animals by zonal ultracentrifugation.